Figure 12: Granule size distribution at various bed temperatures. (FIGURE IS COURTESY OF THE AUTHORS)
|
The granules formed at higher bed temperatures (e.g., 64 and 68 °C) and are more closely bound by a thicker and smoother binder
layer (see Figure 11). At higher bed temperatures, the amount of lumps increased because of the binder's slow solidification
rate (see Figure 12). Consolidation might have occurred in this case because the particles were allowed to move and pack closer
as the binder remained molten for a longer period. The granules formed in this way are perhaps stronger because of their lower
porosity. However, the faster binder solidification rate induced at a lower bed temperature might have encouraged a faster
solid bridge formation, which could in turn lead to weaker bonding and thus produce a more friable granule. Such granules
are more likely to break; therefore, the rate of solid bridge rupture might have increased. In contrast, the slower binder
solidification rate induced at higher bed temperature might have caused the liquid bridge to rupture more easily than the
solid bridge (16). However, the ruptured liquid bonds are still capable of causing further aggregation, which has probably
produced granules with hardly any surface breakages.
Conclusion
The authors studied various formulations and experimental conditions of fluidized hot-melt granulation for preparing granules
of cinnarazine with PEG 6000 as a melt binder. The concentration of PEG 6000 had no significant effect on in vitro drug release profile, but particle size of PEG 6000 slightly changed the in vitro drug-release profile. Both variables influenced the granules' physical properties such as ungranulated fines and size. Increased
granulation time led to an increased granule size. Increasing the fluidization velocity resulted in a decreasing mean granule
size, because of the increase in the number of collision between particles. At bed temperatures higher than the melting point
of the binder, granules had greater strength. However, defluidization of the powder bed was a difficulty at higher temperatures
and also produced lumps. Granule size also increased at higher temperatures. At lower bed temperatures, granules with lower
strength were produced that could not withstand the fluidization air pressure and broke into very small granules or fines.
Therefore, fluidized hot-melt granulation has been proven to be a viable means of producing granules of cinnarazine with PEG
6000 as a melt binder, without the use of solvents or water.
Rakesh P. Patel, PhD,* is an assistant professor and head of the pharmaceutics and pharmaceutical technology department at S. K. Patel College of
Pharmaceutical Education and Research, Ganpat Vidyanagr, Kherva, India 382711. Ajay Suthar is a postgraduate at the department of pharmaceutics of S.K. Patel College of Pharmaceutical Education and Research, raka_77us@yahoo.com
*To whom all correspondence should be addressed.
Submitted: Nov. 3, 2008. Accepted: Dec. 11, 2008.
What would you do differently? Submit your comments about this paper in the space below.
References
1. G.M. Walker, G. Andrews, and D. Jones, "Effect of Process Parameters on the Melt Granulation of Pharmaceutical Powders,"
Powder Technol.
165, 161–166 (2006).
2. C.C. Sun and D.J.W. Grant, "Effects of Initial Particle Size on the Tableting Properties of L-lysine Monohydrochloride
Dehydrate Powder," Int. J. Pharm.
215, 221–228 (2001).
3. T. Abberger, "Influence of Binder Properties, Method of Addition, Powder Type, and Operating Conditions on Fluid Bed Melt
Granulation and Resulting Tablet Properties," Pharmazie
56 (12), 949–952 (2001).
4. T. Schaefer and A. Seo, "The Effect of Droplet Size and Powder Particle Size on the Mechanisms of Nucleation and Growth
in Fluid Bed Melt Agglomeration," Int. J. Pharm.
249 (1), 185–197 (2002).
|
